The proposed Project includes a complex interplay of both microbicide product development with three classes of novel microbicide candidates, as well as microbicide science advancement in which the three classes of active microbicides will be utilized as tools to better understand how an effective microbicide must act. The product development components consist of three classes of compounds with well documented microbicide potential that may be developed as single or combination agents utilizing gels and/or intravaginal rings that will allow long lasting microbicides to be developed and deployed. We believe the potential advancements in product development (new agents, long lasting delivery technology) and microbicide science (pharmacodynamics, in vitro and ex vivo modeling, effects of seminal and vaginal fluids, acceptability testing methods for long lasting and combination products) make this proposal both inherently novel and important to the field of microbicide science in regard to the development of the next generation of microbicide products. In whole, the Project also provides a new model for the performance of Core functions by adding important assay development objectives to improve the ability to effectively prioritize microbicide development. The Administrative Core will play a critical and essential role in ensuring the smooth integration of the various Projects and Cores included in this cooperative agreement research program. The successful performance of this Project requires a high degree of communication and interaction between the various Projects, the Cores, and the Corporate Partner. The Administrative Core will be responsible for managing and enhancing this constructive and synergistic interplay between the participating scientific groups.